The Effect of Clozapine on Self-reported Duration of Sleep and Its Interaction With 23 Other Medications: A 5-Year Naturalistic Study.
Mitchell, Simon P
Dodwell, David JF
Mann, Louisa M
Deakin, Julia B
Syed, Zahoor H
Praseedom, Asha S
Journal of clinical psychopharmacology
Lippincott, Williams & Wilkins
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Fernandez-Egea, E., Chen, S., Jenkins, C., Turrion, C., Mitchell, S. P., Dodwell, D. J., Mann, L. M., et al. (2021). The Effect of Clozapine on Self-reported Duration of Sleep and Its Interaction With 23 Other Medications: A 5-Year Naturalistic Study.. Journal of clinical psychopharmacology, 41 (5), 534-539. https://doi.org/10.1097/jcp.0000000000001432
Background: Sedation is a common and incapacitating clozapine side effect, but the factors associated with and its pharmacological management remain poorly studied. Methods: We conducted a retrospective cohort study based on de-identified electronic clinical records of clozapine-treated patients from the secondary mental health care provider for Cambridgeshire and Peterborough, UK. We first evaluated cross-sectionally the influence of clozapine dose, clozapine and norclozapine plasma levels on self-reported hours slept, as a proxy for sedation, using bivariate correlation and then the longitudinal effect of changes in clozapine dose and other 23 medications using linear mixed effect models. We followed 241 clozapine-treated patients for 56 months on average, with 2,237 face-to-face assessments in total. Results: Patients slept for a mean of 9.35 hours/day, with 46% reporting 10 or more hours per day. Cross-sectionally, sleep duration did not correlate with clozapine dose (r=.14, p=.106), but clozapine plasma levels (r=.38, p< 0.0001) and norclozapine plasma levels (r=.25, p=.005). Longitudinally, the final mixed-effects model revealed four pharmacological variables that had a significant impact on hours slept: clozapine, risperidone augmentation, and atenolol were associated with increased sleep, whereas aripiprazole augmentation was associated with decreased sleep. We found that 20 other psychotropic medications measured were not associated with changes in sleep when added to clozapine. Somnolence is a clozapine level-dependent side effect. Conclusions: The impact of different augmentation strategies might help clinicians to decide on the most adequate strategy, albeit further studies should confirm our results.
This study has not received direct funding. Clinical Research Database (CRD) was supported by intramural grant by National Institute Health Research – Cambridge Biomedical Research Centre (NIHR-BRC-1215-20014); the views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.
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External DOI: https://doi.org/10.1097/jcp.0000000000001432
This record's URL: https://www.repository.cam.ac.uk/handle/1810/319622
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